POS0773 AUTOANTIBODIES IN A MULTI-INSTITUTIONAL INDIAN COHORT (INSPIRE) OF SLE PATIENTS: PREVALENCE, CLUSTER ANALYSIS AND PHENOTYPE ASSOCIATION
Authors: A. Aggarwal, R. Gupta, R. Chatterjee, V. Negi, B. K. Das, P. Ghosh, D. Danda, V. Shobha
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic Lupus Erythematosus (SLE) is characterized by an array of autoantibodies. Different autoantibodies have been associated with different clinical features like anti-dsDNA antibodies with nephritis and anti-phospholipid antibodies with pregnancy loss. However, the prevalence of autoantibodies has been variable across different ethnic groups. Data on the Indian population is limited. Objectives To assess the prevalence of different autoantibodies in a multi-institutional cohort (INSPIRE) of Indian SLE patients and to test their association with various clinical features using cluster analysis Methods The patients (n=1053) enrolled in a multi-institutional cohort of Indian patients (Indian SLE inception cohort for Research [INSPIRE]) were included. 1 Antibodies were assayed using Immunoline (Euroimmune, Germany) 17 antigen kit. Anti-phospholipid antibodies (IgG and IgM anti-cardiolipin antibodies (ACLs), IgG anti-Beta 2 GpI antibodies) were measured using ELISA (Euroimmune). Lupus anticoagulant was available in a subset of patients. The prevalence data for autoantibodies were analyzed using an intensity of only ++ and above on Immunoline assay as significant. Univariate analysis by Chi-square test was done to identify associations between individual autoantibodies and their clusters with clinical manifestations. Results The clinical features were fever in 702, alopecia in 813, oral ulcers in 628, acute cutaneous lupus (ACLE) in 520, proteinuria in 400, pleural effusion in 181, thrombocytopenia in 250 and autoimmune hemolytic anemia in 137 patients. The prevalence of various autoantibodies by ELISA was anti-dsDNA antibodies in 70.2% (551/784), IgG Anti- beta-2 GpI in 4.47% (42/938), IgG ACL in 6.14% (61/992) and IgM ACL in 7.1% (54/760). Lupus anticoagulant was present in 13.9% (112/ 805). By Immunoline assay, the prevalence for anti-Ro 52, anti-Ro 60, anti-La and anti-Ribosomal P was 28.49%, 33.14%, 10.07% and 24.03% respectively (Table 1). Table 1. Prevalence of different autoantibodies in the INSPIRE lupus cohort S. No. Autoantibody Prevalence (%) (n=1053) 1. dsDNA 28.11 2. Nucleosomes 27.83 3. Histones 24.88 4. Ro_52_SSA 28.49 5. Ro_60_SSA 33.14 6. SSB-La 10.07 7. Ribosomal P 24.03 8. nRNP 36.75 9. Sm 33.14 10. Scl-70 3.23 11. PM-Scl 0.38 12. Jo-1 0.09 13. CENP-B 0.38 14. PCNA 1.33 15. AMA-M2 2.28 Cluster analysis (Figure 1) revealed association (Odds ratio with 95% confidence interval) of Cluster 1 (antibodies against dsDNA, histones and nucleosomes) with arthritis (1.51 [1.18-1.94]), proliferative nephritis (3.05[2.08-4.48]) and pleural effusion (1.49[1.08-2.05]), cluster 2 (antibodies against Sm, nRNP, Ro52, Ro60 and Ribosomal P) with ACLE (1.3[1.02-1.65]) and non-proliferative nephritis (1.64[1.09-2.46]) and cluster 3 (antiphospholipid antibodies) with thrombocytopenia (3.34[1.57-7.11]). Figure 1. Cluster analysis of autoantibodies (Cluster 1: dsDNA, histone and nucleosome; cluster 2: Sm, nRNP, Ro52, Ro60 and Ribosomal P; cluster 3: cardiolipin, β2GP1 and La and lupus anticoagulant; cluster 4: Scl-70, Jo-1, PCNA, AMA-M2, PM-SCL and CENP-B) Conclusion The prevalence of anti-Sm antibody and Anti-Ribosomal P antibody is higher whereas that of anti-La antibody is lesser in the Indian SLE patients as compared to other cohorts of SLE patients with different ethnicities. 2 Cluster analysis reveals co-occurrence of different autoantibodies in our patients and their significant association with various clinical manifestations which suggests a possible pathogenic role of autoantibodies or a common genetic basis for it. References [1]Shobha V, Aggarwal A, Rajasekhar L, Jain A, Gupta R, Das B, et al. Indian SLE Inception cohort for Research (INSPIRE): the design of a multi-institutional cohort. Rheumatol Int. 2021 May;41(5):887-894. [2]Yang J, Xu Z, Sui M, Han J, Sun L, Jia X, et al. Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy. PLoS One. 2015 Oct 14;10(10):e0140441. Disclosure of Interests Amita Aggarwal: None declared, Ranjan Gupta Grant/research support from: Dr. Ranjan Gupta has received 2 grants for educating patients and primary care physicians about rheumatoid arthritis managment., Rudrarpan Chatterjee: None declared, Vir Negi: None declared, Bidyut Kumar Das: None declared, Parasar Ghosh: None declared, Debashish Danda: None declared, Vineeta Shobha: None declared